Allele Publication Explains cGMP Generation of Induced Pluripotent Stem Cells

The discovery that adult somatic cells can be reprogrammed to pluripotent stem cells has given the biomedical community a powerful platform for personalized medicine. However, the translation of cell therapies from bench to bedside holds a significant challenge. Realizing the clinical potential for stem cells requires their production under current Good Manufacturing Practice (cGMP) regulations enforced by the FDA. A new protocol (http://onlinelibrary.wiley.com/doi/10.1002/cpsc.18/abstract) published by scientists at Allele and detailed in this quarter’s issue of Current Protocols in Stem Cell Biology, reveals key conditions required for converting adult fibroblasts to induced pluripotent stem cells (iPSCs) under cGMP regulations.¹

The patent-pending protocol is an update to a previous protocol that describes how to reprogram fibroblasts to iPSCs using mRNA. “The system of using mRNA to reprogram fibroblasts presents itself as a very favorable candidate for generating iPSCs for cell therapy” according to the senior author of the paper and CEO of Allele, Dr. Jiwu Wang, “our company is committed to developing stem cell based therapies using this protocol and through the establishment of our own stem cell GMP facilities here in California”. mRNA transfection is “footprint free”, meaning no insertions or alterations have been made to the genome. Transfection of mRNA is also “cleanup free,” because mRNA transcripts are supplied to the cells in the culture medium only for the time required to induce pluripotency. Furthermore, genomic analyses of iPSCs reprogrammed using mRNA indicate that this method of conversion is unlikely to introduce problematic mutations.²

The new version of the protocol describes reprogramming technology that utilizes all cGMP-certified reagents and vessels, meaning that every material is manufactured under guidelines that allow for ancillary use in manufacturing processes related to cell therapy. All materials described in the protocol – from cell medium and components to the coating for tissue culture plates – were meticulously evaluated at every step of generating and storing iPSCs. For truly cGMP produced cell lines, all processes should take place in certified cleanrooms with qualified equipment and thoroughly trained operators.

Establishing a cGMP process for any product intended for human use is a daunting undertaking. Unlike drugs and small-molecule pharmaceuticals, stem cells are living entities whose production cannot be chemically synthesized. Therefore, special considerations must be made – particularly for making individual cell lines – to help assure the highest safety and quality of downstream stem cell products. Adhering to cGMP regulations infuses high quality into the design and manufacturing process at every step. Through rigorous testing, researchers at Allele have identified critical parameters for generating iPSCs from fibroblasts that are cGMP-compliant, and are optimistic that the methods described in this recent publication will serve as a launch pad for the development of future cell products and therapies.

 

1. Ni Y, Zhao Y, Warren L, Higginbotham J, Wang J. cGMP Generation of Human Induced Pluripotent Stem Cells with Messenger RNA. Current Protocols in Stem Cell Biology,2016; 39:4A.6.1-4A.6.25.
2. Bhutani K, Nazor KL, Williams R, et al. Whole-genome mutational burden analysis of three pluripotency induction methods. Nature communications. 2016;7:10536.

Allele GMP CRO and Cell Therapy

Tags: Allele Therapeutics, CA company, CIRM, GMP, iPSC, stem cell therapy